"Human embryonic stem cells created from adult tissue for first time," The Guardian reports, while the Daily Mail's front page leads with the somewhat fanciful warning that new research raises the "spectre of cloned babies".

These headlines are based on newly published research into the use of a technique known as somatic cell nuclear transfer (SCNT) as part of embryonic stem cell research. It should be noted that no babies were born as a result of this research, and the researchers had no intention of producing a live cloned human being.

SCNT involves taking donated egg cells from women and removing their genetic material. These are then fused with human cells – in this case skin cells – and the fused cell begins behaving in a similar way to an embryo by producing human stem cells.

This research is the first time the technique has been successful using human cells.

When these stem cells were tested, researchers found that the cells were able to develop into other types of cells in a manner similar to that seen in stem cells derived directly from embryos.

The researchers say that this could have exciting implications. The technique could potentially be used to take skin cells from a patient to create "personalised" stem cells. The resulting stem cells could then possibly be used to repair damaged tissue, or even treat genetic conditions.

However, there remain ethical concerns over the implications of using SCNT to develop stem cells. These concerns, as well as scientific and financial considerations, will need to be taken into account as this field continues to develop.

Where did the story come from?

The study was carried out by researchers from Oregon Health and Science University (OHSU) and Boston University School of Medicine in the US, as well as Mahidol University in Thailand. It was funded by OHSU, the Leducq Foundation and the US National Institutes of Health, and was published in the peer-reviewed journal, Cell.

Media coverage of this study was as varied as people's feelings are about stem cell research. It ran from the medically hopeful headline of The Independent ("Human cloning breakthrough raises hopes for treatment of Parkinson's and heart disease"), to a straight-to-the-facts headline from The Guardian ("Human embryonic stem cell created from adult tissue for first time"), to fear and controversy from the Daily Mail ("New spectre of cloned babies: Scientists create embryos in lab that 'could grow to full term'").

Despite its headline and further warnings of "designer babies", the Daily Mail does provide a quite useful figure outlining the process the scientists used in the research.

What kind of research was this?

This was a laboratory study that aimed to produce embryonic stem cells from adult skin cells. Embryonic stem cells are unique in that they are able to develop (or differentiate) into other types of cells. Because of this, it is thought that they could play a critical role in the treatment of a wide variety of diseases.

Researchers have been looking into ways of using a patient's own cells to create embryonic stem cells, as this would ensure that the genetic material in any cells used therapeutically would match the patient's DNA. In theory, this should prevent the body from rejecting the cell.

The researchers report that previous attempts to produce embryonic stem cells using this technique have failed, as the cells stopped dividing before they reached an advanced enough stage. During their experiments, researchers identified two reasons for this inability to sufficiently grow the cells and developed techniques to overcome these limiting factors.

Laboratory studies are necessary for developing techniques and procedures that may one day lead to new medical therapies.

This study will no doubt be very exciting for researchers working with stem cells, but we're still a long way from the findings of this study being translated into new treatments for conditions such as Parkinson's disease or heart disease.

What did the research involve?

The researchers used a technique called somatic cell nuclear transfer (SCNT) to transfer genetic material from adult human skin cells into a human egg cell in order to produce embryonic stem cells. SCNT has been used to clone animals before, and is thought to have potential applications in the study and treatment of human diseases.

SCNT involved taking the nucleus (the part of a cell containing most of the genetic information) from a person's skin cells, inserting its cells into a donor's unfertilised egg cell that had its nucleus removed. The skin cell nucleus was then fused with the donor egg cell. Once this happened, the person's genetic material was in a vehicle that was theoretically able to divide.

Researchers then optimised methods to prompt the egg cell to start and continue to divide using electricity and chemical compounds, including caffeine.

Once this cell division yielded approximately 150 cells – a stage called a blastocyst – researchers were able to isolate the embryonic stem cells. The researchers then tested these stem cells to see if their genetic material retained any traces of the genetic material from donor egg cell's nucleus. They also tested whether or not the embryonic stem cells were able to develop into other types of cells.

What were the basic results?

The researchers were able to use SCNT to generate human embryonic stem cells. These cells were found to match the nuclear genetic material of the person's skin cells, and did not contain any trace of the donor egg's nuclear genetic material.

The embryonic stem cells were able to develop into several different types of cells, including heart cells. They were also found to express genes similar to those expressed by embryonic stem cell lines derived following IVF procedures, which the researchers referred to as "genuine" embryonic stem cells.

How did the researchers interpret the results?

The researchers say that this study represents the first successful attempt at generating human embryonic stem cells following somatic cell nuclear transfer.

They say that the observed ability for these embryonic stem cells to develop into heart cells demonstrates their potential use in regenerative medicine.

Conclusion

This research represents the first time that human embryonic stem cells have been developed using the "cloning technique" known as somatic cell nuclear transfer (SCNT).

It is important to note that this study did not attempt to clone a human being by creating a baby in a lab. It is unclear at this point whether the cells in this study would continue to stably divide in a manner sufficient for an embryo to develop to full-term.

While this study is certainly a breakthrough for researchers in the field, its findings are unlikely to translate quickly into regenerative medicine or other medical therapies.

There are some scientific limitations to the approach, including the fact that only a fraction of the fused cells were able to divide sufficiently to reach the blastocyst stage and, of those that did, not all were able to generate stable embryonic stem cell lines.

It is also worth considering that donated egg cells from women are required before SCNT can be carried out, potentially limiting the ability of scientists to generate stem cells on an "industrial" basis.

SCNT does not represent the only approach to embryonic stem cell development. Researchers around the world continue to investigate several methods for developing and using stem cells. It is not immediately clear how the current research will fit into this field, or whether it will trigger a major shift in stem cell research.

In addition to these scientific hurdles, there are ethical and financial considerations that will likely need to be addressed.

Despite these issues, this research does represent a breakthrough in the use of SCNT in the stem cell research field and has implications for disease research.

What the study emphatically does not represent is an impending expansion into cloning babies.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Human embryonic stem cells created from adult tissue for first time. The Guardian, May 15 2013

Embryonic stem cells: Advance in medical human cloning. BBC News, May 15 2013

New spectre of cloned babies: Scientists create embryos in lab that 'could grow to full term'. Daily Mail, May 15 2013

Cloning breakthrough by US scientists. The Daily Telegraph, May 15 2013

Stem Cells Made From Cloned Human Embryos. Sky News, May 15 2013

Cloned babies fear as stem cells are created from skin. Daily Express, May 16 2013

Links To Science

Tachibana M, Amato P, Sparman M, et al. Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer. Cell. Published online May 15 2013

The Daily Mail claims a study has found a ‘Vampire treatment that rejuvenates ageing hearts’.

But before you go to grab your cloak and false pointy teeth, the research it reports on was actually in mice.

The study looked at possible ways to treat age-related cardiac hypertrophy – when the muscles of the heart become thickened, leading to a corresponding decrease in functioning ability.

Researchers joined the blood circulation of pairs of young and old mice. And one month later they looked at the resulting effects on the animal’s heart muscle.

They found that old mice who shared blood with young mice had reduced levels of cardiac hypertrophy compared to similar mice not treated with ‘young blood’.

The researchers suggest that this could be due to a chemical called growth differentiation factor 11 (GDF-11), which is high in the blood of young mice, and could help repair tissue damage.

An obvious limitation of the study is that results in mice do not always apply to humans. In humans, heart failure is where the heart cannot pump enough blood to meet the body’s needs, and this can have many different causes.

Thickening of the heart muscle is just one type of heart failure, which can be caused by high blood pressure, but can also be an inherited condition.

It is difficult to know to what extent the same growth factor could be responsible for heart muscle thickening in people with this type of heart failure. Also, its relevance – if any – to other types of heart failure (for example due to muscle damage following heart attack, due to an abnormal heart rhythm, or due to heart valve disease) is even less clear.

The findings are of scientific interest but are not going to miraculously reverse the entire disease process of heart failure in humans.

Where did the story come from?

The study was carried out by researchers from the Harvard Stem Institute and other research institutes in the US, and was funded by the American Heart Association, Glenn Foundation and National Institute of Health.

The study was published in the peer-reviewed scientific journal: Cell.

The Mail over-interprets the findings from this animal research. It is also unclear where the sub-headline ‘could be ready for use in clinical trials within 4 years’ has come from.

What kind of research was this?

The researchers say that loss of normal heart function leading to heart failure is one of the most debilitating diseases of ageing.

In particular, they discuss the type of heart failure that is often caused by high blood pressure, where the heart muscle becomes thickened and stiff (cardiac hypertrophy) so the heart chambers cannot dilate so well and fill with blood. This is known as ‘diastolic’ heart failure, as it relates to a problem when the heart is trying to refill with blood (diastolic), rather than contract (systolic).

The researchers suggest that animal studies have previously shown that chemicals circulating in the body of a young animal have been shown to restore function to the skeletal muscle of an old animal.

This process was done by what is called ‘parabiosis’ where two animals are surgically joined and so share their blood circulation.

The current animal study aimed to use a parabiosis model to try and reverse the thickening of heart muscle.

What did the research involve?

For their experiments the researchers used old mice (aged about two years) and young mice (aged two months). They used parabiosis to surgically join the blood circulation of pairs of old and young mice.

After they had been joined for one month, the researchers analysed samples from the heart muscle of the mouse pairs.

For comparison they also looked at the effect of shared blood circulation between young-young and old-old mice pairs.

They also compared with a ‘sham’ parabiosis where they surgically joined the tissue of pairs of young and old mice (at the knee joint), but without sharing their circulation.

To look into what could be the cause of any observed effects upon heart muscle, they also intensively monitored the blood pressure of mice while they were joined, and looking at levels of different chemicals in the blood of young and old mice.

What were the basic results?

The researchers found that the effect of surgically combining the circulation of the young and old mice pairs was clearly visible. The hearts of old mice that had their circulation joined to a young mouse looked much smaller and were less heavy than those of old mice who had been joined to old mice.

When they looked at the heart muscle cells under the microscope they found that the cells of old mice joined to young mice had a significantly smaller cross-sectional area than those of old mice joined to old mice, or those in the ‘sham’ parabiosis condition where their circulation hadn’t been joined to the young mice.

The effect of parabiosis on heart muscle cells was similar in both male and female old mice.

Meanwhile, the heart muscle cells of the young mice were no different in any of their three combinations (young-young, young-old or sham parabiosis).

They also carried out a number of experiments into what could be having the observed effects.

They ruled out that the smaller heart muscle cells of the old mice could have been caused by a reduction in their blood pressure. This was because all of the joined mice actually showed increases in their blood pressure compared to before they were joined. 

They also considered the possibility that the changes could be due to behavioural change from the physical constraint of being joined to another mouse, rather than any effect of the shared blood.

However, if this was the case then it would be expected the heart muscles of old mice in the sham parabiosis would also have decreased in size, and they had not.

Overall, the researchers considered the effects could be due to some chemical in the shared circulation. Separately analysing the blood from young and old mice they found that several components of their blood are different. In particular, levels of a molecule called growth differentiation factor 11 (GDF-11) are found to be lower in the blood of older mice.

When they went on to treat the heart muscle cells from rats with GDF-11 in the laboratory, they found that GDF-11 prevents the thickening of the heart cells. In a further experiment involving older female mice, the hearts of a group injected with GDF-11 were significantly lighter and the cells were significantly smaller than those of a group injected with a placebo.

How did the researchers interpret the results?

The researchers’ animal experiments suggest that the thickening of heart muscle can be influenced at least in part by certain chemicals circulating in the blood. They suggest that GDF-11 could reverse thickening of heart muscle, and so conclude that ‘at least one component of age-related diastolic heart failure is hormonal in nature and reversible’.

Conclusion

This study finds that sharing the circulation of young and old mice appears to reverse the age-related thickening of heart muscle cells in the older animal, and it seems this could be due to a certain growth factor in the blood of the young animal. The findings will be of scientific interest, and further our understanding of the processes of heart ageing in animals.

However, the findings have very limited direct relevance to humans, and do not suggest a new treatment for heart failure.

It is also certainly unknown at this point whether increasing levels of this factor in the blood of people with this type of heart failure would somehow reverse the entire disease process. Its relevance to other types of heart failure not associated with thickened heart muscle is even less clear.

Even if further research were to demonstrate that this growth factor could have a potential role in heart failure treatments in humans; joining the circulation of young people with those with heart failure in the manner used in this study is clearly not a possibility.

If the chemical were to be extracted from donor blood, or synthetically produced, there would still be many safety issues to considered, even if the treatment were found to have an effect.

Overall the research does not suggest a new treatment for heart failure in humans, though it may represent the first step towards a possible treatment at some point at the future.

However, due to the uncertainties discussed above it is impossible to estimate the likelihood of this prediction becoming fact.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

The vampire treatment that 'rejuvenates' ageing hearts: Dose of young blood can reverse life-threatening thickening of organ. Daily Mail, May 10 2013

Links To Science

Loffredo FS, Steinhauser ML, Jay SM, et al. Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy. Cell. Published online May 9 2013

Most of the UK media are reporting on a worrying new strain of bird flu in China – the H7N9 strain of the bird flu virus.

According to the media, virology experts at a recent press conference warned that the virus "should not be taken lightly". This warning was prompted by new genetic research into the disease and by news that the virus is thought to have killed 24 people and infected at least 126 in China.

Public health authorities in the UK are reportedly on the alert to watch for any spread of the disease out of China. However, the H7N9 flu virus is currently thought only to be spread between birds and from birds to people.

It is possible that H7N9 could mutate (change) so that it can spread from person to person. This is why experts are investigating this disease, with a view to reducing the effects of a global flu pandemic (similar to the swine flu pandemic in 2009–10).

The new genetic research indicates that the virus might have evolved from at least four other flu viruses circulating in wild bird populations, ducks and domestic chickens. The study also found that H7N9 has already evolved into two separate strains since its emergence.

At the moment there is no need to panic and the risk to anyone living in the UK is only theoretical. But international health authorities will need to keep a careful watch on the spread of this new strain.

Where did the story come from?

The study was carried out by researchers from the Chinese Academy of Sciences in Beijing and the Chinese Centre for Disease Control and Prevention. It was funded by several public institutions in China, including the Ministry of Science and Technology.

The study was published in the peer-reviewed medical journal The Lancet.

The UK coverage of the study and press conference was accurate, with most news sources highlighting the need for vigilance rather than blind panic.

What kind of research was this?

This was a genetic analysis of the H7N9 bird flu virus, in which scientists used information taken from global virus databases to track the potential origins of the virus, as well as any genetic changes in the virus that have taken place since it emerged.

The authors point out that the H7N9 virus causing human infections was identified in China at the end of March 2013. As of April 18, the virus had spread to six provinces and cities, with 87 people infected and 17 fatalities. While this seems a worryingly high mortality rate, it is too early to say how this might change if the virus were to mutate to enable it to spread from person to person (rather than from bird to human as is currently the case).

Preliminary analyses have shown that the H7N9 virus causing the current outbreak in China may have originated from a number of existing flu viruses in wild birds, ducks and poultry. All bird flu influenza A viruses have a genome (genetic make-up) consisting of just eight single segments of RNA. But it is often the genetic simplicity of viruses that makes them so contagious.

One of these RNA segments codes for the protein haemagglutinin (HA), and another segment codes for another protein, neuraminidase (NA), both of which are crucial in helping the virus spread from cell to cell and from organism to organism.

HA and NA are present on the surface of the virus. HA plays a key role in the entry of the virus into a cell, and NA is involved in the release of the virus from the host cell.

The HA and NA proteins can be classified into different subtypes, which gives rise to the familiar HxNy classification of influenza viruses, where x stands for one of 17 possible subtypes of HA, and y stands for one of 10 NA subtypes.

What did the research involve?

Scientists used information taken from global virus databases to compare the H7N9 genome to other related flu viruses.

They carried out a detailed genetic analysis that enabled them to construct evolutionary (or phylogenetic) 'trees' – the viral equivalent of a family tree – for all eight RNA fragments of the virus. This allowed them to see what the current virus could have evolved from.

The researchers also tried to determine how the particular assortment of RNA particles present in the current H7N9 virus could have arisen, using genetic information. This was done to assess where the virus originated from geographically and the type of animal it had originally infected.

What were the basic results?

When two different types of bird flu virus infect the same cell at the same time, the new virus produced by the host cell can contain a mix of the RNA particles from each virus, generating new types of virus. This process is called reassortment.

The scientists concluded that the new H7N9 virus appears to have originated from at least four reassortment events.

The HA gene might have originated from a bird flu virus that normally infects ducks and the NA gene might have come from a virus that affects migratory birds, which may then have infected a duck. The other genes might have come from two different viruses that affect chickens. The reassortment of these genes could have occurred in ducks or chickens.

By comparing different samples of H7N9, the authors also noticed two genetically distinct strains of the virus, implying that it has already evolved further since it emerged.

How did the researchers interpret the results?

The researchers say the results suggest that the HA genes of the H7N9 virus were originally circulating in the East Asian fly way – a major route used by migratory birds spanning East Asia.

The NA genes seem to have been introduced by birds migrating from Europe, transferring to ducks in China via the East Asian fly way.

The six remaining RNA segments of the virus (referred to as internal genes) appear to have originated in two different groups of H9N2 viruses infecting chickens and ducks in eastern China. 

The researchers say that the most recent common ancestor of the H7N9 virus was probably in existence around January 2012, a time when migratory birds would have been wintering in areas of mainland China near to where the H7N9 outbreak has occurred. 

They stress the need for “extensive surveillance” of the virus in human beings, poultry and wild birds. Further evolution of the virus has the potential to make it more harmful to humans, either by making people more ill when they catch it, or by increasing its ability to transmit between humans, or both.

In a linked article in the Lancet, Dr Marc Van Ranst and Philippe Lemey of the University of Leuven, in Belgium, add that the history of the virus may be particularly important, because the low severity of the virus in birds probably allowed it to spread silently in domestic and wild birds. “Containing this hidden epidemic may prove very challenging given the magnitude of the domestic and wild bird populations in China,” they say.

Conclusion

This is important research tracking the origins of the new H7N9 bird flu virus, which gives some clues about how it might behave in the future. Scientists are particularly concerned that a future mutation could mean it is transmitted between humans, which increases the risk of a pandemic (an epidemic of infection across countries or continents).

For travellers to China and other countries affected by bird flu, it's important to observe the following precautions:

• avoid visiting live animal markets and poultry farms
• avoid contact with surfaces that are contaminated with animal faeces
• don't eat or handle undercooked or raw poultry, egg or duck dishes
• don't pick up or touch dead or dying birds
• always follow good personal hygiene practices, including washing your hands regularly

Read more about reducing your risk of bird flu when travelling in affected countries.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

H7N9 bird flu is a 'serious threat' - researchers warn. BBC News, May 1 2013

New bird flu poses "serious threat", scientists say. Reuters, May 1 2013

Deadly bird flu poses 'real global threat to humans. Channel 4 News, May 1 2013

GPs advised how to spot bird flu as virus continues to mutate at an alarming rate. Mail Online, May 1 2013

Deadly Bird Flu Is Global Threat, GPs Warned. Sky News, May 1 2013

Deadly H7N9 bird flu strain could mutate into 'very serious' global threat, warns expert. Daily Express, May 1 2013

Links To Science

Liu D, Shi W, Shi Y, et al. Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses. The Lancet. Published online May 1 2013

“Taller, skinnier women have evolved to have more babies than their shorter counterparts,” the Mail Online website has claimed.

It reports on research examining the characteristics of women in two villages in the west African nation of The Gambia over more than 50 years.

Researchers were interested in whether recent trends for decreased mortality and fertility rates in human populations over time may influence natural selection on other traits. They analysed records of just under 3,000 women between 1956 and 2010 to find their body mass index (BMI) and number of births.

Initially, women who were shorter and with higher BMIs were more likely to reproduce successfully, but over time the reverse became true. The study did not investigate the reasons for this, but the researchers suggest that improvements in healthcare are changing the relationship between height, BMI and health in The Gambia.

Other factors could also play a role, including cultural changes (such as men’s changing preferences for sexual partners). Due to the highly specific sample population in the study, we can't say whether these trends in height, BMI and adult fertility would be found in UK women.

The wider implications of the study are that it suggests that evolution, driven by natural selection, is not just something that happened to our ancestors. It can still have a significant influence on the human population.

However, due to the highly specific sample population in the study, it is difficult to assess whether the findings would relate to women in the UK. Analysis of similar data would be required to determine whether this was the case.

Where did the story come from?

The study was carried out by researchers from various research centres in Germany, the UK, The Gambia, and the US.

The collection of the data analysed in the study was funded by the UK Medical Research Council, and the researchers were funded by various bodies, including the Wellcome Trust and the European Research Council.

The study was published in the peer-reviewed journal Current Biology.

Despite this being a study conducted in The Gambia, the Mail Online illustrated the story with a picture of German model Heidi Klum (who has four children).

And the Mail Online's headline, “taller, skinnier women have evolved to have more babies than their shorter counterparts”, is not strictly correct. The study did not find that being taller and having a lower body mass index are evolutionary adaptations that enable women to have more children. The fact that over time taller women with lower BMIs in the Gambia had a reproductive advantage over shorter women with higher BMIs is likely to relate to other factors such as what women’s height and BMI say about their health.

What kind of research was this?

This was a longitudinal study looking at the evolutionary consequences of changes in the characteristics in a population over time, in this case in The Gambia.

The researchers say that human populations have recently shown declines in both mortality (death) and fertility rates and that the evolutionary consequences of this have not been extensively investigated. In particular, they looked specifically at how the changes influenced variation in the population in ‘relative fitness’ in evolutionary terms (essentially how able individuals are to reproduce successfully).

The researchers looked at how height and BMI might have influenced this ability to reproduce successfully.

What did the research involve?

The researchers used data that had been collected from women in two rural villages in one district in The Gambia between 1956 and 2010. They collected data for 2,818 women, who together provided a total of 51,909 years of follow-up in total.

The women’s heights and weights had been recorded, and their BMIs calculated. Researchers used methods in their analyses that allowed them to take into account the fact that women’s measurements had not all been taken at the same age, and some women provided more than one measurement at different ages.

Births and deaths were also recorded.

The researchers used an annual measure of ‘fitness’ in the population that assessed how many babies the women had each year. They also assessed how BMI and height related to ‘fitness’, and whether this relationship changed over time.

What were the basic results?

The researchers found that over time, variation in ‘relative fitness’ in the population declined. This was largely as a result of reduction in the variation in survival in early life – with a reduction in deaths among girls before they reached adulthood and had a chance to reproduce. As with most developing countries, child mortality was very high in The Gambia for much of the 20th century – a trend that gradually improved over time.

Survival among girls aged under 15 increased over time and variation in relative adult fertility increased at the same time.

There was a change in how height and BMI related to adult fertility in the Gambian population. Taller women initially had lower adult fertility, but over time they showed higher adult fertility. Women with a higher BMI initially had higher adult fertility, but by the end of the study period they showed lower adult fertility. So initially, up to 1974, women who were shorter and with higher BMIs (height less than 157cm and BMI greater than 21) reproduced more, after 1975 women who were taller and with lower BMIs (height greater than 158cm and BMI less than 21) reproduced more. The researchers’ analyses suggested that the relationship may have been influenced by healthcare improvements that affected how health related to height and BMI.

How did the researchers interpret the results?

The researchers concluded that their findings show the changes in selective pressures on humans over time. They say that the findings suggest that changes in the characteristics of human populations and social, culture, medical and economic environment are likely to modify but not remove natural selection in humans. They say that this is likely to be increasingly driven by changes in culture – particularly in medical practice and public health measures.

Conclusion

This study provides insight into changes in how height and BMI have related to female reproductive fitness in The Gambia over a long period of time. While the general evolutionary principles identified in this study may apply to populations worldwide, the specific findings as they relate to height, BMI and reproductive fitness may not. Analysis of similar data from other populations would help to determine whether this was the case.

A key limitation of this research is that the women’s heights and BMIs were not all measured at the same age or on a regular basis. The researchers note that if they had annual measurements of the women’s heights and BMIs this would have allowed a more detailed look at the relationship between these factors and reproductive fitness.

Overall, the study provides interesting insight into how selection in humans changes as population characteristics and our complex social, culture, medical and economic environment changes. However, these findings are likely to be of more interest from an evolutionary perspective than a medical one. Shorter women with higher BMI should not be unduly alarmed by this news.

However, being underweight or overweight can affect your chances if you are trying to conceive.

Find out more about how to protect your fertility.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Taller, skinnier women have evolved to have more babies than their shorter counterparts. Mail Online, April 26 2013

Links To Science

Courtiol A, Rickard IJ, Lummaa V, et al. The Demographic Transition Influences Variance in Fitness and Selection on Height and BMI in Rural Gambia. Current Biology. Published online April 25 2013

"New drug-resistant strains of the parasite that causes malaria have been identified," is the worrying news being reported on the BBC News website. Covering the same piece of research, The Guardian outlines the ongoing "scientific detective hunt in Cambodia to find much-needed clues to the development of resistance in the malaria parasite to the life-saving artemisinin drugs".

While most of us are aware of the issue of antibiotic resistance, the growing problem of resistance to antimalarial drugs often goes unreported, at least in the developed world. But the potential impact of increasing antimalarial resistance could be devastating. Our armoury of malarial drugs is limited, so further resistance could lead to a world where malaria is practically incurable.

The "detective hunt" that has hit the headlines involved looking at the genetic make-up of more than 800 samples from Africa and southeast Asia of the malaria-causing parasite Plasmodium falciparum (P. falciparum).

Three genetically different subpopulations showed resistance to artemisinin drugs, the medication that is the basis of current treatments for P. falciparum malaria. This suggests that resistance can be caused by different genetic variations.

Researchers will now go on to look more closely at the genetic variations they identified to see which ones contribute towards artemisinin resistance. The researchers hope that these findings and subsequent research will help us better understand how resistance to antimalarial drugs develops, with the ultimate aim of being able to eliminate the resistant strains of the parasite.

Where did the story come from?

The study was carried out by researchers from several international research centres, including the University of Oxford. It was published in the peer-reviewed journal Nature Genetics and was funded by the Wellcome Trust, the UK Medical Research Council Division of Intramural Research, the US National Institutes of Health, and the Howard Hughes Medical Institute.

Scientists already knew that artemisinin-resistant strains of malaria existed in western Cambodia, but they did not know much about its genetic make-up.

The research was generally well reported by the BBC and The Guardian.

What kind of research was this?

This was a laboratory study looking at the genetic make-up of different strains of the malaria parasite Plasmodium falciparum collected from different parts of Asia and Africa. There are several different types of malaria parasite, but P. falciparum is the most common and causes the most severe malaria infections. Some strains of the P. falciparum parasite have evolved resistance to antimalarial drugs such as artemisinin, one of the main drugs used to treat this type of malaria.

Drug resistance occurs through genetic changes in the parasites, making them less susceptible to the drugs used to kill them. Essentially, "survival of the fittest" evolutionary pressure leads to the increased spread of resistance over time.

When the drug is used on mixed populations of the parasite, some of which have resistance, the resistant parasites are more likely to survive than the non-resistant parasites. This means their genes spread through the population, causing the resistance to spread.

The researchers report that successive waves of this drug resistance originated in western Cambodia. Resistance to artemisinin and related drugs is now reported to be well established in this area. They wanted to look at whether the genetic make-up of P. falciparum from western Cambodia could give clues about why this might be the case.

What did the research involve?

The researchers analysed the genetic make-up of 825 samples of P. falciparum collected from 10 areas in southeast Asia (including four areas in Cambodia) and west Africa. They focused on more than 86,000 single "letter" variations at sites throughout the DNA code of the parasite. Once they identified which letter each of the samples had at these sites, they used a computer programme to analyse how the different samples were likely to be related to each other.

For example, the programme estimates which strains are joined by a common "ancestor" strain and how closely the strains are related. These relationships are shown as a "family tree" which joins all of the samples together.

The researchers also looked at resistance of these parasite samples to the drug artemisinin. They analysed data on how quickly the parasites were cleared from patients' blood when treated with an artemisinin derivative drug called artesunate.

What were the basic results?

The researchers found that within a relatively small area of western Cambodia there were several distinct subpopulations of P. falciparum that had an unusually high level of genetic differences. This finding was surprising, as researchers would have expected the samples from a small area to be more genetically similar than they were.

Three of these subpopulations showed resistance to the antimalarial drug artesunate. Within each subpopulation there were high levels of genetic similarity, suggesting that they had high levels of recent inbreeding.

The researchers identified a number of single letter variations among the artemisinin-resistant strains. Some of these variations lay within genes and would have an effect on the proteins that the genes encoded (carried the instructions for making). These changes could be responsible for the resistance to artemisinin-derived drugs. For example, some of these changes were in genes responsible for repairing the DNA if it gets damaged. Researchers thought this might relate to how quickly these strains in western Cambodia developed DNA mutations and resistance to antimalarial drugs.

How did the researchers interpret the results?

The researchers conclude that their findings provide a framework for further investigations into how artemisinin resistance arises. They say that these discoveries suggest that there could be multiple forms of artemisinin resistance because multiple subpopulations of resistant parasites were discovered, each with different genetic characteristics.

Conclusion

This study provides researchers with more information about the genetic make-up of different subpopulations of a type of malaria parasite taken from Africa and southeast Asia called P. falciparum, which causes the most severe malarial infections. They were surprised by the high levels of genetic diversity in parasite samples from western Cambodia, an area where resistance to a number of antimalarial drugs has developed and then spread.

Some of these Cambodian subpopulations showed resistance to the antimalarial drug artesunate. Data about their genetic variations will now be investigated further to see exactly which of these variations could be contributing to this resistance, and how.

The researchers speculate that historical, as well as genetic, factors may also have been involved. Parts of Cambodia were historically very isolated in terms of human movement due to the civil war between government forces and the Khmer Rouge, as well as poor roads in forested mountain areas. This could have created pockets of isolation ideal for parasitical inbreeding.

In addition, in the 1950s and 1960s there was mass administration of the antimalarial drugs chloroquine and pyrimethamine in one area in western Cambodia, leading to a strong selection pressure for strains resistant to these drugs.

It is hoped that these findings and subsequent research will help us better understand how resistance to antimalarial drugs develops, with the ultimate aim of being able to eliminate these resistant strains so that we can continue to treat the disease.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Parasite 'resistant to malaria drug artemisinin'. BBC News, April 29 2013

Malaria resistance - it's in the parasite's genes. The Guardian, April 28 2013

Links To Science

Miotto O, Almagro-Garcia J, Manske M, et al. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nature Genetics. Published online April 28 2013

Scientists have discovered a gene that "could rejuvenate old hearts" according to The Daily Telegraph. The newspaper goes on to say that "damaged hearts could be regenerated simply by switching off a gene which prevents cells from dividing".

Some parts of our body, such as our skin, are made up of cells that divide and reproduce throughout our lives to produce new tissue. This is known as mitosis. Other parts, such as the heart, are thought to lose this ability shortly after birth.

The Telegraph story is based on new research in mice that has identified a specific gene – dubbed the ‘heartbreak gene’ by the Mail Online – called Meis1 that appears to block the heart tissue’s ability to regenerate.

The researchers found that using various techniques to ‘switch off’ the Meis1 gene did lead to the production of new heart cells in mice.

The hope is that similar techniques could be used in humans to repair damage to the heart that can occur in cases of heart failure.

But switching off a gene to treat a progressive disease like heart failure is unlikely to be quite as simple as the Telegraph suggests. Much more research is needed before we may see a groundbreaking new treatment capable of healing ‘broken hearts’.

Where did the story come from?

The study was carried out by researchers from the University of Texas Southwestern Medical Center in the US, Ain Shams University in Egypt and the University of Queensland in Australia. The research was funded by the American Heart Association, the Gilead Sciences Research Scholars Program in Cardiovascular Disease, the Foundation for Heart Failure research and the US National Institutes of Health.

The study was published in the peer-reviewed journal Nature.

The media reporting of this research was generally accurate, despite some confusion from Mail Online about a "rogue gene" that stops "heart cells dividing uncontrollably".

Most importantly, the media headlines should not be interpreted to mean that “revolutionary new treatments” are on the horizon. The idea of using genes to treat disease – gene therapy – has been around since the 1970s. But, currently, there is only one licensed medication on the market that makes use of gene therapy techniques.

What kind of research was this?

This was animal and laboratory research that aimed to identify and describe the process that controls the generation of new heart cells in newborns. Newborns are able to produce new heart cells to replace injured cells. However, this ability is lost early in life (generally by seven days after birth), and the adult heart lacks this regenerative capacity.

Previous research has suggested that a gene called Meis1 is involved in the development of the foetal heart, and may be involved in regulating the regeneration of newborn heart cells. The researchers thought that this gene may also play a role in the loss of this regenerative capability.

Several heart conditions lead to damage or death of heart cells and to heart failure, where the organ is unable to pump enough blood around the body.

The adult heart is not able to generate new cells to repair such injury and heart failure is considered to be a progressive disease (gets worse over time). So any technique that could reverse this progressive decline would be welcome.

But as an animal study, any results should not be assumed to apply directly to people. Significant further research is needed to determine whether the mechanisms identified in this study provide a suitable target for addressing human heart failure or other causes of heart damage.

What did the research involve?

The researchers carried out a series of experiments to define the role of Meis1 in regulating the generation of new heart cells.

They first measured expression levels of the gene to determine how these levels changed during the first seven days of life (after which the heart is no longer able to produce new cells). Gene expression is the process through which the information encoded in our genes is used to produce proteins. Measuring the level of gene expression shows how active the gene is.

They next investigated the effect on heart cell generation of removing the Meis1 gene, using both rat heart cells as well as mice models.

The mice lacking a copy of the Meis1 gene were compared to control mice (which had copies of the gene) on several factors, including:

• changes in the production of new heart cells
• characteristics of the heart cells
• the size and function of the heart

These comparisons were made for newborn as well as adult mice.

Next, the researchers increased the expression of Meis1 to determine whether doing so produced an effect on the generation of new heart cells in mice.

Finally, they carried out a series of tests to determine how the Meis1 interacted with other parts of the system to identify the mechanism by which the gene controls heart cell generation.

What were the basic results?

The researchers found that there was an increase in Meis1 expression over the course of the first week of life, and that this expression continued into adulthood.

When Meis1 was removed, the researchers found that rat heart cells were able to produce new cells. Mice lacking the Meis1 gene exhibited a similar increase in the production of new heart cells.

Fourteen days after birth (which corresponds to one week after the heart typically stops producing new cells) these mice had hearts of similar size and function to control mice that retained the Meis1 gene. The researchers found that the hearts of mice lacking the Meis1 gene had significantly more cells that those of the control mice, and that these heart cells were smaller in size compared with controls.

When investigating the effect of the Meis1 gene of the adult mouse heart, the researchers found that heart size and function were normal in these mice at both four weeks old and at seven months old. There was also no difference in the size of the heart cells.

The mice lacking the Meis1 gene continued to produce new heart cells into adulthood, but the rate at which they produced these cells slowed as they aged.

The researchers found that newborn mice engineered to overexpress Meis1 did not generate new heart cells in response to injury, while control mice hearts regenerated normally.

Finally, the study authors identified several interactions between Meis1 and other genes in the system that controls the production of new heart cells. They found that when Meis1 is deleted, there is increased activity among some genes that promote the generation of new heart cells. There was also a corresponding decrease in the activity of genes that normally inhibit the production of these new cells.

How did the researchers interpret the results?

The researchers conclude that Meis1 is a critical component of the system that regulates the production of new heart cells. They say their research suggests that cell cycle arrest in the adult human heart (whereby the heart no longer generates new cells) may, theoretically, be reversed.

Conclusion

This research identifies a possible mechanism that leads to the inability of the adult heart to repair itself. It is premature to suggest that the study heralds a new era in treating heart failure.

As with much early stage cell and animal research, this study is probably most useful for scientists and suggests future research paths that may be helpful in the quest to treat heart conditions. It is too early to tell, however, whether the Meis1 gene will prove to be a useful target for future therapies, let alone whether treatments targeting the gene or its products will be safe and effective enough for treating heart failure patients.

Current treatments for heart failure, while a lot better than they used to be, are only of limited effectiveness. So the message is still that prevention is better than cure.

Effective ways you can reduce your risk of heart failure include:

• quit smoking if you smoke
• maintain a healthy weight
• eat a healthy diet
• take plenty of exercise

Read more about reducing your heart failure risk.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Gene could rejuvenate old hearts. The Daily Telegraph, April 17 2013

'Heartbreak gene' which stops organ recovering after injury discovered by scientists: Breakthrough could lead to revolutionary new treatments. Mail Online, April 18 2013

Links To Science

Mahmoud AI, Kocabas F, Muralidhar SA. Meis1 regulates postnatal cardiomyocyte cell cycle arrest. Nature. Published online April 17 2013

“Couch potatoes can't help being lazy – they were born that way,” claims the Mail Online website. 

As this is such a sweeping statement, it may be a surprise to readers that the science behind this headline was based entirely on rats and involved no human participants or gyms.

Researchers bred two distinct groups consisting of ‘lazy rats’ (rats that showed little to no interest in running in a wheel) and ‘active rats’ (rats that appeared to be highly motivated to run).

At the end of the 10-generation breeding programme, a series of tests was run to see if there were significant genetic differences between the two groups.

The researchers did find a number of genetic differences. However, in the main, the results were mostly inconclusive and did not shed much light on the potential biological causes for the differences in rats, let alone humans.

Even if the results were more ‘earth shattering’, an obvious limitation is that humans are vastly different to rats. Reasons for someone choosing to exercise is unlikely to be purely down to their genes.

So the immediate implications to humans are minimal. The headline is speculative and not supported by the research in question.

Where did the story come from?

The study was carried out by researchers from the University of Missouri (US) and was funded by a grant from the College of Veterinary Medicine at the University of Missouri and funds from the College of Veterinary Medicine’s Development Office.

The study was published in the peer-reviewed American Journal of Physiology.

The Mail’s reporting of this study was largely speculative and the implications to humans overstated. This was a relatively inconclusive rat-based study that was presented in the headlines as a relatively conclusive study of immediate relevance to humans. This isn’t the case in reality.

While the research is of some value – it at least proves that it is possible to selectively breed ‘lazy rats’ – it was not conclusive and its immediate practical relevance to humans is minimal. 

The headlines claiming “Couch potatoes can't help being lazy – they were born that way” and “genes play major role in deciding whether we enjoy a trip to the gym or not” are not backed up by the science behind it.

What kind of research was this?

This was an animal-based study examining the characteristics of rats that had been selectively bred to show high and low levels of voluntary running behaviour.

Rats with vastly different voluntary running behaviour were used to mimic the human condition whereby increasingly large swathes of the population are voluntarily inactive, while some remain very active.

As the study involved running voluntarily, the researchers hoped it may give clues to the origins of motivation to exercise.

Rat studies are often used, as the short lifespan of a rat means researchers can selectively breed a characteristic of interest (e.g. high voluntary running activity) in a relatively short space of time.

This allows researchers to mimic equivalent human evolutionary pressures, such as the shift from most people being physically active for much of the day to a more sedentary lifestyle. The equivalent study in humans would take decades, or possibly even hundreds of years.

Both rats and humans are mammals, so findings in rats usually give a sense of what might be happening in humans and forms the basis of further theories and explanations. But there is no guarantee that what is found in rats will be found in humans and this is why studies on humans are important.

What did the research involve?

The researchers started with 159 rats. When they were adults (28 days old) they were introduced to running wheels and the distance they ran voluntarily was monitored for six days.

After this period the 26 rats (13 males and 13 females) with the highest voluntary average running distances were separated from the rest and allowed to mate. This was repeated for 10 generations and subsequently selecting the top 26 voluntary runners in each generation.

Similarly, at the other end of the spectrum the 26 lowest voluntary runners were also selectively bred in the same way for 10 generations.

This ultimately led to two distinct, selectively bred groups of rats – ‘active rats’ and ‘lazy rats’

At the end of this process the researchers analysed aspects of the active rats and compared them with the lazy rats in an attempt to uncover what lay behind the differences in voluntary running characteristics. Factors that were studied included:

• muscle characteristics in the hind limbs (the main muscles the rats use for running)
• body fat and muscle composition
• the way genes were switched on and off (gene expression) in the nucleus accumbens: a part of the brain thought to be associated with reward, motivating activities (e.g. running), as well as addictive behaviour such as drug addiction
• gene expression in the muscles

The main analysis compared the characteristics between the active and lazy groups.

What were the basic results?

After 10 generations of breeding, the voluntary running distances (measured as an average distance on days five and six of a six-day running window) were 8.5 times greater in male active rats than male lazy rats (9.3km vs 1.1km, p<0.001). The difference in female rats was 11.0 times greater (15.4km vs 1.4km, p<0.001).

The active rats also ran faster and for significantly longer for both sexes.

The researchers thought physical inactivity might be a result of larger body weights causing the rats to exercise less. However, they actually found running patterns were not related to differences in body weight.

No differences were found for the amount of food eaten, body fat percentage or weight gained between the two groups. This may appear slightly odd as one might expect the runners to eat more to balance the energy expenditure of running, or to be thinner if they didn’t eat more.

No significant differences in hind limb muscle characteristics were observed between the groups.

The analysis of gene expression in the brain uncovered eight gene transcripts that were expressed differently between the groups (that is, having a greater than a 1.5-fold difference).

The top differences were related to genes the researchers described as involved in “cell morphology, cell death and survival, dermatological diseases and conditions” as well as “nervous system development and function, cell signalling, and molecular transport”. They did not go into further detail.

How did the researchers interpret the results?

The researchers concluded that their selectively bred rats “can potentially be used to further study low motivation for voluntary running and any other phenotype [characteristic] co-selected along with this trait”.

The researchers discussed the possibility that certain brain signalling pathways may explain some of the reasons behind differences in voluntary exercise, but these were largely speculative.

They highlighted their finding that “increased fat mass alone was not a factor driving lower voluntary running distances”, as previous research had suggested a causal link between having more fat and being less inclined to exercise. This was in addition to the stronger relationship in the other direction, that is, less active people have more fat as a result.

Conclusion

This small study provides future animal researchers with a unique and interesting group of rats to study genetic factors behind differences in levels of voluntary exercise. Through selective breeding, the researchers produced a group of rats that were highly motivated to run and another group that were not. The current study did not shed much light on the potential biological causes for the differences in voluntary exercise behaviour, but did provide a solid base for their study in the future – in rats at least.

The findings in these selectively bred rats have limited immediate relevance to humans. However, further research into the genetic basis of motivation to exercise based on this preliminary work may potentially lead to implications for humans, although this is likely to be a long way off.

The research findings themselves are very limited in telling us any reasons for the differences in the high and low running groups. However, they did observe a small selection of genetic differences that could provide a rough clue as to what was different in the two groups.

These genetic differences require a lot more research to confirm if they are indeed involved or important in exercise motivation in rats. Yet more studies would then be needed to see if similar genetic factors were present or important in humans. There is no guarantee that the differences found in rats will be found in humans – humans have to be studied directly to be sure.

The reasons why someone chooses to exercise or not is unlikely to be entirely down to their genetic make-up. It is likely that there are a wide range of underlying factors including cultural and psychological, as well as individual circumstances.

While this research may of be of interest to animal behaviourists and the like, its immediate implications to humans are minimal and were overstated by the media.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Couch potatoes can't help being lazy – they were born that way. Mail Online, April 9 2013

Links To Science

Roberts MD, Brown JD, Company JM, et al. Phenotypic And Molecular Differences Between Rats Selectively-Bred To Voluntarily Run High Versus Low Nightly Distances. American Journal of Physiology. Published online April 3 2013

Most of the UK media have reported on what has been described as landmark research into the genetics of breast, ovarian and prostate cancer. Many commentators state that this will lead to cheap and reliable screening tests for the cancers within "five years".

The news is based on the results from the Collaborative Oncological Gene-environment Study (COGS), which is an international collaboration involving hundreds of researchers. It looked at the genetic markers of more than 200,000 people to detect genetic variants that were associated with an increased risk of three types of cancer:

• breast cancer 
• prostate cancer 
• ovarian cancer

Previous research has identified genetic mutations that can increase the risk of breast cancer, such as the BRAC1 and BRAC2 mutations. The latest research identified more than 70 new variants, located in specific areas of human DNA (known as positions or loci), that are associated with an increased risk of breast, prostate and ovarian cancer, including 41 loci that are associated with increased risk of breast cancer.

This research does have the potential to lead to more accurate screening for certain types of cancer using relatively simple and cheap DNA testing, such as saliva or blood tests. But claims that these tests are “five years away” could be premature. It remains to be seen what effects these new insights into the genetics of cancers will actually have.

Where did the story come from?

An international team of researchers is participating in the Collaborative Oncological Gene-environment Study (COGS). COGS is a European Union funded project, with additional funding from Cancer Research UK and the US National Institutes of Health.

COGS has today published 13 papers in five journals. Several of the papers have been published together in a special iCOGS Focus issue of Nature Genetics, along with commentaries and a guided tour of the research. All of this is open access, meaning that it is available for free from the Nature Genetics website.

In this story we will be concentrating on the identification of 41 new genetic regions associated with breast cancer.

This study was led by researchers at the University of Cambridge and funded by Cancer Research UK and the European Community. It was published as part of the iCOGS Focus issue in the peer-reviewed journal Nature Genetics.

Much of the news reporting concentrates on the possibility of using the results of these studies to design a genetic test for cancer. It is possible that future cancer screening could be improved by the use of genetic information – for ‘risk-stratification’, which is determining how great someone’s risk of developing cancer is. However, it is likely that such a programme would be complex, and the issue of how genetic data will be stored and used will have to be addressed.

It also remains to be seen whether routine screening using gene testing would be affordable or cost-effective. So claims that genetic screening for cancer is five years away could be premature.

What kind of research was this?

This was a case-control study that aimed to identify genetic variations that increased the risk of developing breast cancer.

What did the research involve?

The researchers were looking at what are known as single nucleotide polymorphisms or SNPs.

The human genetic code (human genome) is made up of information contained within our DNA. This sequence is made up of strings of molecules called nucleotides, which are the building blocks of DNA.

SNPs occur when the DNA sequence varies by a single nucleotide. Some SNPs have been associated with significant effects on human health.

While the entire COGS project looked at SNPs thought to be associated with prostate, ovarian and breast cancer, the study we are analysing just looked at breast cancer.

SNPs associated with risk of breast cancer were identified by combining the results of nine previous studies. The researchers investigated whether these SNPs were present more frequently in people who developed breast cancer by comparing 45,290 people of European ancestry who developed breast cancer with 41,880 who did not.

What were the basic results?

Variations in the DNA sequence at 27 different positions (loci) in the genome have previously been found to be associated with breast cancer risk. In this study, all but four of these previously identified loci showed clear evidence of association with breast cancer in this study (three others showed weaker association, and the other one was not investigated).

In addition, the researchers identified 41 new loci that were statistically significantly associated with the risk of breast cancer. Each locus was associated with a small increase in risk of breast cancer.

The researchers estimate that the 41 newly associated loci explain approximately 5% of the familial risk of breast cancer.

The researchers also state that a larger number of loci could contribute to susceptibility to breast cancer, suggesting that 1,000 additional loci are involved in breast cancer susceptibility.

How did the researchers interpret the results?

The researchers conclude that they have identified “more than 40 new susceptibility loci, more than doubling the number of susceptibility loci for breast cancer”.

The researchers go on to state that “the currently known loci now define a genetic profile for which 5% of the female population has a risk that is [equivalent to] 2.3-fold higher than the population average and for which 1% of the population has a risk that is [equivalent to] 3-fold higher”.

Conclusion

This interesting research has identified 41 new genetic loci that are associated with increased risk of breast cancer. Other studies performed by the COGS identified a further eight genetic loci, which, combined with the 27 previously identified loci, brings the total identified to 76. This is in addition to mutations in ‘high risk’ genes such as BRAC1 and BRAC2.

This research has the potential to lead to genetic profiling that may aid in identifying women at an increased risk of developing breast cancer (as well as women at increased risk of ovarian cancer and men at increased risk of prostate cancer).

However, it is likely that such a programme would be complex because, in addition to genetic testing, the results would have to be integrated into a risk assessment process, and care pathways for people in different groups would have to be developed. The issue of how genetic data would be stored and used would have to be addressed. Therefore, it seems unlikely that genetic screening will be introduced in the near future.

Nonetheless, this remains important and impressive research. Any advances in our understanding of the genetics of cancer are valuable and the study could be the first step to improving screening programmes for breast, ovarian and prostate cancer. It may also improve our knowledge of these diseases, and aid in the design of prevention and treatment strategies. But much more work will need to be done to reach these goals.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Links To The Headlines

DNA test reveals 80 markers for inherited cancer risk. BBC News. March 27 2013

Genetic testing for prostate and breast cancer comes a step closer. The Guardian, March 27 2013

Breakthrough? Scientists unveil the 'single biggest leap forward' in tackling prostate cancer. The Independent, March 27 2013

Genetic screening for cancer 'within five years'. The Daily Telegraph, March 27 2013

The £5 test that predicts the risk of cancer - and it could be available on the NHS within five years. Daily Mail, March 28 2013

£5 test could spot patients with biggest risk of cancer. Daily Express, March 28 2013

Cancer Detection: DNA Study Brings 'New Era'. Sky News, March 27 2013

Links To Science

Michailidou K, Hall P, Gonzalez-Neira A, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nature Genetics. Published online March 27 2013

"Having an older grandfather 'raises autism risk'," the Daily Telegraph reports, saying that older fathers are much more likely to go on to have grandchildren with autism. However, this doesn't mean men should change their plans for having a family.

The association between fathers' ages and the likelihood of their children having autism has been seen before. This news comes from a study suggesting that the link may go back another generation. Men who had a son or daughter later in life were more likely to have a grandchild diagnosed with autism when compared with men who became fathers in their early twenties.

This association was particularly clear for men who had children after the age of 50. The odds of having a grandchild with autism increased by 67% when looking at the age of the child's father's father, and 79% when examining the age of the child's mother's father.

The researchers speculate that the association seen in the study may be caused by mutations in men's sperm cells that develop as they grow older, and that a certain proportion of these mutations may have an indirect impact on autism in later generations. But despite their findings, the researchers say that, "older men should not be discouraged to have children".

A single cause for autism, such as genetics, is unlikely. Several interacting risk factors for autistic spectrum conditions have been proposed. We don't yet know precisely what causes autism, so there's no need to plan when to have children based on the results of studies like this.
 

Where did the story come from?

The study was carried out by researchers from the Karolinska Institute in Sweden, King's College London, Mount Sinai School of Medicine in the US, and the University of Queensland in Australia. The research was funded by the Swedish Research Council, the Swedish Council for Working Life and Social Research, and the Karolinska Institute.

It was published in the peer-reviewed medical journal JAMA Psychiatry.

The research was covered appropriately in the media, with both BBC News and The Daily Telegraph pointing out that the results do not mean that older people should be discouraged from having children. The chances of a child being born with autism are quite small, despite more alarming figures of a 67-79% relative increase.

What kind of research was this?

This was a case-control study using data from patient records in Sweden. The study assessed the association between paternal age and autism among grandchildren.

As a case-control study, this research can only describe associations between age and autism risks two generations later. It cannot tell us conclusively that one causes the other, and can only speculate as to possible causes underlying the association.

What did the research involve?

Using the Swedish Patient Registry, researchers identified a large group of individuals diagnosed with childhood autism between 1987 and 2009 (the cases) and another group of individuals with no autism diagnosis (the controls).

Five controls were selected for each autism case, and were matched to the individual with autism according to gender and exact year of birth.

This means that if a boy born in 1995 was diagnosed with autism during childhood, the researchers selected five other boys born in 1995 who were not diagnosed with autism.

Autism was diagnosed by specialists and conformed to international definitions that excluded Asperger's syndrome.

For each of the case and control children, the researchers used the Swedish Multi-generation Register to collect data on the parents' ages at the time of the child's birth, as well as information on their grandfathers' ages at the time of their parents' birth.

Data from three generations was used in the analyses:

• child's autism status (the main outcome)
• parents' ages at the child's birth
• grandparents' ages at the parent's birth

The researchers used this data to estimate the association between the age of a grandfather at the parent's birth and autism in the child. Two separate analyses were carried out:

• the first assessed the impact of maternal grandfather age (that is, the grandfather's age when the child's mother was born)
• the second assessed the impact of paternal grandfather age (the grandfather's age when the child's father was born)

They analysed grandfathers' ages separately by those:

• less than 20 years old
• 20 and 24 years old (referent group)
• 25 to 29 years old
• 30 to 34 years old
• 35 to 39 years old
• 40 to 44 years old
• 45 to 49 years old
• more than 50 years old

The odds of having a grandchild with autism were calculated for each grandfather age band. This was compared with the odds seen among grandfathers who were between 20 and 24 years old when the child's parent was born. This calculation provides an idea of the association between increasing grandfather paternal age and autism in the grandchild.

Several other variables (confounders) were included in the analysis to control for their affect on the relationship, including:

• a family history of schizophrenia, bipolar disorder or autism
• parental educational attainment (as a marker for the child's socioeconomic status)
• place of residence

What were the basic results?

The original study included 9,868 children with an autism diagnosis and 49,340 children with no such diagnosis (the controls). Due to missing data on parental age among the parents and grandparents, as well as parental educational attainment, only 5,933 of the original cases (60%) and 30,904 of the original controls (63%) were included in the statistical analyses.

Men who had a daughter when they were younger than 20 years or between 25 and 29 had no significant difference in odds of having a grandchild with autism compared with men who had a daughter when they were between 20 and 24 years old.

At older ages, however, the odds of having a grandchild diagnosed with autism increased with increasing age. Compared with those aged between 20 and 24 when the child's mother was born, the odds of having a grandchild diagnosed were:

• 19% higher among those aged 30 to 34 years (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.07 to 1.32)
• 31% higher among those aged 35 to 39 years (OR 1.31, 95% CI 1.15 to 1.49)
• 31% higher among those aged 40 to 44 years (OR 1.32, 95% CI 1.12 to 1.54)
• 34% higher among those aged 45 to 49 years (OR 1.34, 95% CI 1.07 to 1.67)
• 79% higher among those aged 50 years or more (OR 1.79, 95% CI 1.34 to 2.37)

A similar pattern emerged when analysing the association between paternal grandfather age and childhood autism. Compared with men who were 20 to 24 at their son's birth, the odds of having a grandchild with autism were:

• not significantly different among those aged less than 20 years (OR 0.91, 95% CI 0.73 to 1.12)
• 10% higher among those aged 25 to 29 years (OR 1.00 to 1.20)
• 17% higher among those aged 30 to 34 years (OR 1.17, 95% CI 1.05 to 1.30)
• 15% higher among those aged 35 to 39 years (OR 1.15, 95% CI 1.02 to 1.31)
• 23% higher among those aged 40 to 44 years (OR 1.32, 95% CI 1.05 to 1.44)
• 60% higher among those aged 45 to 49 years (OR 1.23, 95% CI 1.30 to 1.97)
• 67% higher among those aged 50 years or more (OR 1.67, 95% CI 1.25 to 2.24)

How did the researchers interpret the results?

The researchers concluded that a "grandfather's age is associated with risk of childhood autism, independent of paternal or maternal age", and that their results "provide new information about the paternal age effect and its effect on future generations".

Conclusion

The large study suggests that there is an association between a grandfather's age at the birth of his daughter or son and the diagnosis of autism in his grandchild. This research raises interesting questions surrounding the genetic components of autism spectrum disorders. But the study cannot in itself explain what may underpin this relationship.

The researchers suggest several possible explanations for the links between paternal age and childhood autism. These include the association being caused by "an increase rate of mutations in the sperm of older men", or that it could be explained by other variables such as "men with mental or personality disorders being more likely to become fathers at older ages". However, this study did not test either of these possible explanations.

Previous research has suggested that a father's age when his child is born is associated with an increased risk of autism in his children. Analyses of the data used in the current study support that finding. The main analyses in this current report further suggest that a grandfather's age when his child is born is also associated with an increased risk of autism in his grandchild.

However, it's worth noting the limitations of this study. While there were a large number of cases and controls included in the data analysis, they represent only 60-63% of the original group of participants. This is a fairly high drop-out rate, and may bias the results if those whose data was not available differed from those included in the analysis in important ways.

For example, data on grandparental age may have been harder to come by for older grandparents, because older records may be incomplete. The researchers attempted to account for this by carrying out a sensitivity analysis (a statistical technique that attempts to account for uncertainty). They say the results of this analysis indicate that the association was not biased by missing data on grandparental age, but arguably this is more of an educated guess than a certainty.

The researchers conclude that, "older men should not be discouraged from having children based on these findings," an important conclusion that was also reported by the media.

These results may provide interesting insights for researchers as to the possible mechanisms behind the development of childhood autism. However, as we do not yet know what causes the conditions on the autistic spectrum, there is no need to decide whether and when to have a child based on this study.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Having an older grandfather 'raises autism risk'. The Daily Telegraph, March 20 2013

Grandparents 'may relay autism risk to grandchildren'. BBC News, March 21 2013

Older fathers autism link. Daily Express, March 21 2013

Links To Science

Frans EM, Sandin S, Reichenberg A, et al. Autism Risk Across Generations - A Population-Based Study of Advancing Grandpaternal and Paternal Age. JAMA Psychiatry. Published online March 20 2013

"A gene previously shown to be linked to obesity may also increase the risk of a deadly form of skin cancer," BBC News reports. The news comes from a study investigating the genetic factors associated with malignant melanoma, the most serious form of skin cancer.

The study looked at single-nucleotide polymorphisms (SNPs), which are variations in a single nucleotide, or 'letter', of DNA. Some SNPs can have a significant effect on human health and development.

The researchers discovered that several SNPs found in a region of the FTO gene are associated with an increased risk of melanoma. Previous research found that certain variations in the FTO gene may be linked to obesity and body mass index (BMI), as mice with these variations had a tendency to overeat. However, the SNPs identified in this study were in a different region of the FTO gene and are not associated with BMI.

This interesting research suggests that the FTO gene is associated with more than just BMI. However, we can't tell if the variations actually do contribute towards melanoma, or how.

Whatever your genetics, the most important and well-established risk factor for melanoma (and other types of skin cancer) remains overexposure to sunlight and artificial sources of UV light, such as sunbeds and sun lamps. Read more about reducing your melanoma risk.

Where did the story come from?

The study was carried out by a team of international researchers as part of the Melanoma Genetics Consortium, and was funded by a number of sources including the European Commission, Cancer Research UK, the Leeds Cancer Research UK Centre and the US National Institutes of Health.

It was published in the peer-reviewed journal Nature Genetics.

The BBC and the Daily Mail both covered the research accurately.

What kind of research was this?

This was a case-control study where the researchers analysed the genomes of people who developed melanoma (the cases) and the genomes of people without melanoma (the controls).

The aim of the research was to determine whether changes in one base of DNA called single-nucleotide polymorphisms (SNPs) were present more frequently in people with melanoma.

This type of study highlights the association between melanoma and certain SNPs and other variants of DNA, but it cannot prove that these variations cause an increased risk of developing melanoma.

What did the research involve?

The researchers analysed SNPs from people of European origin in 1,353 people with melanoma and 3,566 people without melanoma. They hoped to identify SNPs that were associated with melanoma.

The researchers then looked to see if the SNPs they identified as being associated with melanoma were also associated with melanoma in another group of cases and controls (the replication group). They replicated their findings in 12,314 people with melanoma and 55,667 people without melanoma from Europe, Australia and the US who had European ancestry.

As the SNP the researchers identified was located in a region of the FTO gene that was found to be associated with obesity, the researchers then looked to see if the association still existed after adjusting for BMI. This was so they could rule out the possibility that obesity contributes towards the development of melanoma, and not other FTO gene variants.

What were the basic results?

The researchers initially identified three SNPs in the FTO gene that were significantly associated with melanoma.

One SNP (rs16953002) was associated with 32% increased odds of melanoma (odds ratio (OR) 1.32, 95% confidence interval (CI) 1.17 to 1.50)

This SNP was also associated with melanoma in the replication group of 12,314 people with melanoma and 55,667 people without melanoma (OR 1.14, 95% CI 1.09 to 1.19).

SNPs in a different part of the FTO gene have been associated with obesity. However, the researchers found no significant association between rs16953002 and BMI in the people involved in this study, and the association between rs16953002 and melanoma existed even after BMI was adjusted for.  

How did the researchers interpret the results?

The researchers conclude that they have identified a new region of the genome that is associated with an increased risk of melanoma.

This new region was in the gene FTO. Although variations in this gene have already been found to be associated with BMI, the variations identified in this study were in a different region of the gene and were not associated with BMI. This suggests that FTO could have a wider function than initially thought.

Conclusion

By comparing the genomes of people with melanoma with the genomes of people without melanoma, this study has identified variations in a sequence of DNA that are associated with an increased risk of melanoma.

However, this research does not tell us if the variations in the gene actually contribute towards melanoma. Further research is therefore needed to determine how variations in this gene could play a role in melanoma.

Learning more about the genetics involved in conditions does offer the prospect of discovering new treatments for them, so this is valuable research.

Whatever your genetics, the most important and well-established risk factor for melanoma and other less deadly skin cancers remains exposure to UV light – both natural sunlight and artificial sources of light, such as sunbeds.

Effective ways of lowering your risk of developing melanoma include avoiding exposure to the sun when it is at its hottest (usually between 11am and 3pm), dressing sensibly in the sun, using sunscreen, and never using sunbeds or sunlamps.   

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Fat gene 'linked with skin cancer'. BBC News, March 4 2013

Obesity and deadliest form of skin cancer 'have genetic link'. Daily Mail, March 4 2013

Links To Science

IIes MM, Law MH, Stacey SN, et al. A variant in FTO shows association with melanoma risk not due to BMI. Nature Genetics. Published online March 3 2013